THE SPECIFICITY OF PHARMACOLOGY IN CHILDREN

Pr Gérard Pons

Paediatric and Perinatal Pharmacology, Cochin, "Saint-Vincent de Paul" Hospital, René Descartes University, Paris, France

Too often drug evaluation in children is not available and many drugs are prescribed in an unlicensed or off-label manner. However, extrapolation of the adult doses to children is not appropriate due to differences in both the pharmacokinetics and the pharmacodynamics of drugs with a risk of inefficacy or increased toxicity as shown by the tragedies of the past related to drug exposure of the newborn infant (e.g. chloramphenicol and the grey baby syndrome).

Data on intestinal drug absorption are scarce. Volume of distribution of most drugs is higher in neonates and infants than in adults. At birth, most metabolic bathways are immature. However, some are close to maturity with metabolic profiles different from those in adults. The different metabolic bathways have varying rates of maturation reaching adult level at different ages. For most drugs metabolic rats expressed per unit of body size in infants surpass those in adults. The glomerular infiltration rate and the tubular secretion do not reach the adult values before several weeks of age.

The pharmacodynamics may also be influenced by organ immaturity as suggested by age-related changes in the pharmacokinetic-pharmacodynamic relationship. Some diseases are specific to children and require specific evaluation. Drugs may also disturb growth and maturation in children.

As shown by the different maturational profiles, children cannot be considered as a homogeneous group and paediatric age should be subdivided into different age classes, requiring specific evaluation depending on the potential use of the drug in each of these age classes.

The American government has made legislative changes encouraging industrial companies to study medicines in children and have committed major funding from the US NIH to encourage both clinical trials in children and an increase in scientific knowledge in this age group. There is a need in Europe for legislative changes of funding in this area.